Simultaneous pancreas-kidney transplantation for end-stage renal failure in type 1 diabetes mellitus: Current perspectives

Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.

Pancreas transplantation in type Ⅱ diabetes mellitus

Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has revealed that similar graft and patient survival can be achieved when compared to type 1 diabetes mellitus recipients. A cautious strategy regarding candidate selection may limit appropriate candidates from additional benefits in terms of quality of life and potential amelioration of secondary side effects of the disease process. Although our current understanding of the disease has changed, uniform listing characteristics to better define and study this population have limited available data and must be established.

Exocrine drainage in vascularized pancreas transplantation in the new millennium

The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980 s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder(systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin(systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990 s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion(portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to recreate the natural physiology of the pancreas with firstpass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine theliterature on exocrine drainage in the new millennium(the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period.

Mortality assessment for pancreas transplants in the United States over the decade 2008-2018

BACKGROUND Pancreas transplant is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes.However,since 2005,no comprehensive analysis has compared survival outcomes of:(1)Simultaneous pancreas-kidney(SPK)transplant;(2)Pancreas after kidney(PAK)transplant;and(3)Pancreas transplant alone(PTA)to waitlist survival.AIM To explore the outcomes of pancreas transplants in the United States during the decade 2008-2018.METHODS Our study utilized the United Network for Organ Sharing Standard Transplant Analysis and Research file.Pre-and post-transplant recipient and waitlist characteristics and the most recent recipient transplant and mortality status were used.We included all patients with type I diabetes listed for pancreas or kidneypancreas transplant between May 31,2008 and May 31,2018.Patients were grouped into one of three transplant types:SPK,PAK,or PTA.RESULTS The adjusted Cox proportional hazards models comparing survival between transplanted and non-transplanted patients in each transplant type group showed that patients who underwent an SPK transplant exhibited a significantly reduced hazard of mortality[hazard ratio(HR)=0.21,95%confidence intervals(CI):0.19-0.25]compared to those not transplanted.Neither PAK transplanted patients(HR=1.68,95%CI:0.99-2.87)nor PTA patients(HR=1.01,95%CI:0.53-1.95)experienced significantly different hazards of mortality compared to patients who did not receive a transplant.CONCLUSION When assessing each of the three transplant types,only SPK transplant offered a survival advantage compared to patients on the waiting list.PKA and PTA transplanted patients demonstrated no significant differences compared to patients who did not receive a transplant.

Simultaneous pancreas-kidney transplantation in a single center： 10-year retrospective analysis

Background Simultaneous pancreas-kidney transplantation （SPKT） is the best treatment option for diabetic patients with advanced chronic renal failure. The current study aimed to analyze the surgical indications, treatments and prognosis of SPKT.Methods We retrospectively analyzed 40 cases of SPKT performed between December 1999 and January 2010 in our center, including the survival rate, complications and the reasons of reoperation.Results Of all the 40 SPKT cases, the one-year survival rates of the recipients, kidney and pancreas transplant graft were 97.6%, 97.6% and 92.7%, while 97.6%, 91.1%, 92.7% at 3 years and 83.6%, 78.0%, 79.4% at 5 years, respectively. After SPKT, 10 patients need reoperation because of surgical complications （14 operations）. The reoperation rate was 25%, including 2 patients （4 operations） with hematuria, 4 patients with abdominal hemorrhage, 2 patients （3 operations） with abdominal infection, 1 patient with pancreatic venous thrombosis, 1 patient with anastomotic leakage, and 1 patient with fistula.Conclusion Although SPKT provides a successful and effective treatment for diabetics with end-stage renal disease, how to reduce the complications of this treatment still need further effort.

胰肾联合移植中供体切取和修整的技巧

目的总结胰肾一期联合移植中供体胰十二指肠及肾脏切取及修整的经验。方法回顾性分析19例胰肾联合移植术中供体胰十二指肠及肾脏切取的方法与移植物的修整技巧。结果无1例发生移植物损伤。联合移植术后9d之内18例完全停用外源性胰岛素，空腹血糖正常，尿糖≤（＋）。术后2～4d，血肌酐和尿素氮降至正常。3例出现移植肾脏急性排斥反应，2例发生移植胰腺急性排斥反应，给予甲泼尼龙冲击治疗后恢复正常。1例术后因移植物加速排斥反应，术后11d切除移植胰、肾。结论胰肾联合移植手术中，供体胰十二指肠及肾脏的切取及修整是手术成功的重要因素之一。

移植胰腺病理学诊断标准及其进展

胰腺移植和胰肾联合移植是治疗1型糖尿病和部分2型糖尿病及其并发症导致的肾衰竭的最佳治疗方法。胰腺移植的类型主要包括同期胰肾联合移植(SPK)、肾移植后胰腺移植(PAK)和单纯胰腺移植(PTA)。在所有的胰腺移植类型中,对移植胰腺的活组织检查(活检)仍然是明确诊断其排斥反应并与其他并发症进行鉴别的最佳方法。本文对移植胰腺活检的方法及其相关的研究进展、移植胰腺活检排斥反应诊断标准及其进展、移植胰腺主要的并发症及其病理学表现进行阐述,旨在为指导临床对上述并发症予以准确诊断,良好地保障移植胰腺和受者的长期存活提供参考。

胰肾联合移植治疗糖尿病肾功能衰竭五例临床分析

目的总结胰肾联合移植(SPK)围手术期及出院后随访期处理经验,降低SPK术后并发症发生,提高SPK临床效果。方法回顾性分析2017年11月至2018年10月5例因糖尿病肾功能衰竭接受SPK术受者的临床资料、围手术期及出院后随访期资料。结果5例受者供胰、供肾冷缺血时间均控制在8 h内,围手术期无外科技术性出血、肠瘘、动静脉大血栓、坏死性胰腺炎等并发症发生。1例术后原发性移植肾功能恢复延迟经血液透析后逐渐康复;2例术后因抗凝而发生移植胰腺区域腹腔内渗血,经药物促凝治疗后止血成功,但其中1例导致继发性肾功能障碍,经透析和调整免疫抑制剂剂量后逐渐恢复;1例术后因抗凝而发生消化道出血,经药物促凝治疗后停止;3例术后1周后常规移植物彩色超声检查发现移植胰腺内血管小血栓形成,经抗凝治疗后消失或稳定好转;1例移植肾周积液感染经局麻清创引流后康复;2例术后出现高钾血症经治疗后血钾恢复正常;1例术后第45天突发急性左心功能衰竭,经心肺复苏后恢复自主心率,但意识未恢复,1周后受者家属放弃治疗出院;其余4例受者术后血糖与血肌酐水平完全恢复正常且脱离外源性胰岛素使用与透析,康复出院,其中1例在术后143 d出现急性排斥反应经激素冲击治疗后缓解。随访至2019年3月20日,目前存活的4例受者空腹血糖及血肌酐水平均正常,糖尿病并发症得以缓解或改善。结论SPK是治疗糖尿病肾功能衰竭的有效手段,能使受者脱离胰岛素及维持性透析,改善糖尿病并发症,从而明显提高受者的生活质量。